While mPFC LFP recordings cannot distinguish between PL- and IL-derived activity, the dynamic changes in network synchrony reported here underscore the complex role that the mPFC plays in learning about danger and safety. Work in primates has shown that the dorsal anterior cingulate (dACC), the primate homologue of the rodent PL, adjusts amygdala firing when stimuli switch valence during aversive-reinforcement learning (Klavir et al., 2013). Given the findings presented here, such dACC-toamygdala directionality could account for the safety signal-evoked firing acquired in the primate amygdala during training (Genud-Gabal et al., 2013). Human data accentuate the flexibility of this circuit during learning. Consistent with data from animal models, the dorsal ACC/mPFC are engaged during fear expression and early extinction, while the ventral ACC/mPFC (IL homologue) are active during late extinction (Etkin et al., 2011). On the other hand, safety engages both the dorsolateral PFC (Pollak et al., 2010) and ventromedial PFC (Schiller et al., 2008). Thus, the role of different PFC and ACC subdivisions in safety signaling remains to be elucidated.
